Continuing Review VA Requirements

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Continuing ReviewVA Requirements

• Kevin L. Nellis, M.S., M.T. (A.S.C.P.)
• Program Analyst
• Program for Research Integrity Development and
  Education (PRIDE)

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Topics

• IRB and Investigator requirements of continuing
  review
• IRB approval dates
• Requirements when IRB approval expires

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Continuing Review Research Must be Substantive
and Meaningful

• Includes, but not limited to
• Review of the ongoing level of risks and benefits
• Assessment of the need for special safeguards to
  protect subjects
• Review of the adequacy of ongoing protection for
  potentially vulnerable individuals

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Considerations for Continuing Review

• IRB must conduct continuing review of research at
  intervals appropriate to the degree of risk, but
  not less than once per year 38 CFR 16.109(e)
• IRB must have written procedures for determining
  which projects require review more often than
  annually (38 CFR 16.103(b)(4)(ii)).
• Review may be by the convened IRB or by expedited
  review, if appropriate
• IRB approval criteria must be satisfied

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Investigator Submits Protocol Summary Written
Status Report

• Brief summary of the research methodology
• Number of subjects entered and withdrawn
  (including reason) for the review period and
  since the inception
• Summary of complaints regarding the research
  since the last IRB review
• Gender and minority status of those entered into
  protocol, if appropriate
• Number of subjects considered to be members of
  specific vulnerable populations

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Investigator Submits Protocol Summary Written
Status Report

• Copy of the current informed consent form(s) and
  any new proposed informed consent form(s) along
  with a description of changes in the new form
• Current HIPAA authorization
• List of all amendments since last IRB approval
• Information that may impact on the risk benefit
  ratio, such as SAEs and complaints regarding the
  research

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Investigator Submits Protocol Summary Written
Status Report

• Summaries, recommendations, or minutes of the
  Data Monitoring Committee (DMC) meetings (if
  applicable) or findings based on information
  collected by the data and safety monitoring plan
• Assurance that all identified unanticipated
  internal or local SAEs, have been reported as
  required to the IRB of record
• Summary of all unanticipated problems involving
  risks to subjects or others, and all internal or
  local SAEs

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Investigator Submits Protocol Summary Written
Status Report

• Research findings to date, if available
• Relevant multi-center trial reports
• New scientific findings in the literature, or
  other relevant findings, that may impact on the
  research
• PI statement certifying that all subjects on the
  master list signed an informed consent form prior
  to undergoing any study interactions or
  interventions (unless waived by IRB)

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At Continuing Review

• All IRB members must receive and review a
  protocol summary and a status report on the
  progress of the research
• At least one voting member of the IRB (i.e., a
  primary reviewer) needs to receive a copy of the
  complete protocol, including any modifications
  previously approved by the IRB.
• All IRB members have access to the complete IRB
  protocol file and relevant IRB minutes

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IRB Ensures

• Approval criteria are satisfied
• Informed consent is accurate and complete
• Informed consent form, HIPAA authorization, and
  protocol are consistent
• Significant new findings that may affect the
  subjects willingness to continue participation
  are provided to the subjects

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Expedited Continuing Review

• If expedited, IRB Chair or designee should
  receive and review all documentation and complete
  protocol
• Reminder Determinations and protocol-specific
  findings justifying those IRB determinations must
  be documented in either the IRB protocol file or
  the minutes

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Master List of Subjects

• IRB must ensure that the master list of subjects
  entered into the study contains only those
  subjects who have signed an informed consent form
  (unless waived)
• May rely on assurances from the PI and audits
  conducted by the RCO

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IRB Approval Date Convened IRB

• No Conditions date of the convened IRB meeting
  at which approval was granted
• Minor Conditions date the study was approved
  by the convened IRB contingent on minor
  conditions being addressed (NOT the date that the
  conditions are verified)
• Note Substantive Conditions defer approval

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IRB Approval Date Expedited IRB

• All conditions met date the IRB Chair, or
  experienced IRB voting member(s) designated by
  the IRB Chair, signs IRB approval to the research
  study

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If Approval Expires

• Local research office must promptly notifying the
  investigator
• Investigator must stop all research activities
  including, but not limited to
• Enrollment of new subjects
• Continuation of research interventions or
  interactions with currently participating
  subjects
• Data analysis.

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If Approval Expires

• Investigator must immediately submit to the IRB
  Chair a list of research subjects who could be
  harmed by stopping study procedures.
• IRB Chair, with appropriate consultation with the
  Chief of Staff, determines if subjects on the
  list may continue participating in the research
  interventions or interactions

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If Approval Expires

• Once the study approval has expired, IRB
  re-review and re-approval must occur before the
  study can resume
• The IRB cannot retrospectively grant approval to
  cover a period of lapsed IRB approval

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30 Day Rule

• When continuing review occurs annually and the
  IRB performs continuing review within 30 days
  before the IRB approval period expires, the IRB
  may retain the anniversary date as the date by
  which the continuing review must occur. There is
  no provision for any grace period to extend the
  conduct of research beyond the expiration date of
  IRB approval. Therefore, continuing review and
  re-approval of research must occur on or before
  the date when IRB approval expires.

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Timeline Example Convened IRB - No Conditions

• Convened IRB meets on March 15, 2009 and approves
  the protocol with no conditions
• Continuing review and re-approval of research
  must occur on or before the date when IRB
  approval expires, or March 15, 2010

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Timeline Example Convened IRB - Minor Conditions

• Convened IRB meets on March 15, 2009 and approves
  the protocol with minor conditions
• Investigator completes changes on March 20, 2009
• IRB Chair verifies conditions are met on March
  25, 2009
• Continuing review and re-approval of research
  must occur on or before the date when IRB
  approval expires, or March 15, 2010

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Timeline Example - Expedited IRB

• IRB chair reviews protocol on March 15, 2009 and
  request more information from Principal
  Investigator
• Investigator makes additional changes and
  resubmits protocol on March 20, 2009
• IRB Chair reviews final changes and approves
  protocol on March 25, 2009
• Continuing review and re-approval of research
  must occur on or before the date when IRB
  approval expires, or March 25, 2010

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Timeline Example - 30 Day Rule

• IRB approval of a protocol is set to expire on
  March 25, 2010
• The IRB reviews and approves the protocol at a
  convened meeting on March 15, 2010
• Continuing review and re-approval of research
  must occur on or before the date when IRB
  approval expires, or March 25, 2011

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Key Points

• Continuing review must be meaningful,
  substantive, and timely
• Investigators must submit required information
• Understand timeline for when continuing review
  and approval must occur
• Prevent expiration of IRB approval
• Understand what to do if IRB approval expires

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QUESTIONS